This project seeks evidence of adverse effects associated with environmental exposures using a clinical research approach integrating laboratory and epidemiologic methods. It emphasizes interdisciplinary development of ideas and methodologies coupled with attention to details of both the laboratory procedures and the gathering and analysis of data concerning human subjects. Current effort focuses on the development of techniques for identifying genetic damage and alterations in metabolism associated with human exposure to potentially toxic substances. These techniques are being used in model studies of individuals exposed to known amounts of carcinogenic and mutagenic agents used for cancer chemotherapy, smokers, and individuals accidentally exposed to large quantities of PCBs. These studies are designed to help evaluate and refine assay methods, to investigate mechanisms involved in specific models of human disease, and to investigate the effects of exposures that may be important to public health.